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We have demonstrated in the ANRS 099 ALIZE trial that simplification therapy with once-daily efavirenz (EFZ), didanosine (ddI), and emtricitabine (FTC) in HIV-1 infected adults with viral suppression receiving a protease inhibitor-based regimen was well tolerated and associated with sustained virologic suppression and immunological benefit during 48 weeks (Molina et al, JID, March 2005). Also, adherence to study medications was better with the once-daily regimen than with the PI-based regimen. Finally, there was a significant increase in HDL-cholesterol levels in the once-daily group compared with the PI group.

Because FTC was not available at the end of the trial, patients were offered to continue the study, which was extended for 3 years, and to receive the same once-daily combination

Glucose – Median Change From Baseline (mg/dL)

Baseline Characteristics of Patients Randomized to the Once-Daily Group of the ALIZE Trial

Among the 152 patients (85%) who continued the once-daily combination of FTC+ddI+EFV up to week 48, 147 (83%) were followed until year 3 and 125 (70%) remained on study treatment after 36 months.

During follow-up, the proportion of patients with virologic failure (plasma HIV RNA above 400 copies/mL) at month 36 reached only 6% in the on-treatment analysis and 23% in the intent-to-treat analysis.

The incidence of grade 4 adverse events stabilized after the first 48 weeks of follow-up, since 29 patients (16%) encountered a serious adverse event before week 48, and only 17 (10%) up to 36 months. No patient discontinued study treatment because of worsening of lipoatrophy.

There was a slightly statistically significant increase in plasma glucose level (p<0.05), but the proportion of patients meeting the diabetes melitus definition (glucose > 126 mg/dL) remained very low, between 2 to 5% during follow-up. Interestingly, there was no increase in total cholesterol level or LDL cholesterol after 36 months with this combination. Yet, a significant increase in HDL cholesterol level already observed at week 48 was sustained up to month 36 (+11.6 mg/dL), and 42% of patients (20% at baseline) had a plasma HDL cholesterol level > 60 mg/dL at month 36, a level which is associated with protection against cardiovascular risk.

Of note, the incidence of lipodystrophy (both lipoatrophy and lipohypertrophy) remained unchanged after 36 months of therapy as compared to baseline. This is an interesting result with this new combination.

+5.4 mg/dLp<10-4

1.7 mg/dLp=0.77

To assess the long-term safety and efficacy of a once-daily combination of FTC + ddI + EFV in patients randomized to the once-daily arm of the ALIZE trial and willing to continue therapy with the same combination after week 48 of the trial.

The substitution of a PI-based regimen by a simple and convenient once-daily combination of emtricitabine, didanosine and efavirenz maintained a good suppression of plasma HIV-1 RNA levels and continued increases in lymphocytes CD4+ cell counts for 3 years without worsening of lipodystrophy or metabolic abnormalities.

This study was supported by a grant from ANRS – ALIZE study ANRS trial 099.

We thank Dr. F. Rousseau from Gilead who provided FTC up to the end of the trial.